Epidemiological studies have suggested that exposure to MDMA during adolescence is correlated with a high incidence of subsequent use of other drugs such as cocaine. Animal laboratory studies have shown that drug administration during adolescence leads to different neurochemical and behavioral adaptations than drug administration during adulthood and that the effects of drugs and the factors that mediate drug effects are different in males and females. In addition, both social and environmental factors have been shown to alter the use of illicit drugs by adolescents and drug use during this critical developmental period has long-lasting effects that persist into adulthood. Our preliminary data show that (A) MDMA during adolescence, but not in adults, leads to increased reward associated with cocaine; (B) that social and environmental factors alter the effect of MDMA on cocaine reward in adolescents and (C) that the mediation of cocaine reward by social and environmental factors is different in male and female adolescents. The specific hypothesis of this application is that both social and environmental factors alter the behavioral effects of MDMA and the subsequent response to cocaine and that the behavioral and neurochemical adaptations that occur in response to social and environmental changes are sex-specific. Currently, there is very little information on differences in the mediation of drug effects in males and females during adolescence. A better understanding of the specific effects of social and environmental factors on behavior and neurochemistry altered by MDMA and cocaine in male and female adolescents will lead to novel, possibly age- and sex-specific preventions and treatments for drug abuse.